Spinal Lymphatic Dysfunction Aggravates the Recovery Process After Spinal Cord Injury.

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes.

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

[Expression of CXCR4 and VEGF in hemangioblastomas of the central nervous system and its relation to tumor angiogenesis].

OBJECTIVE: To evaluate the relationships of CXCR4 (chemokine stromal cell-drived factor-1 receptor) and VEGF (vaseular endothelial growth factor) expression to tumor angiogenesis in hemangioblastomas of the central nervous system. METHODS: The protein expressions of CXCR4 and VEGF were detected by SP immunohistochemical staining in 40 hemangioblastomas. The endothelial cells of blood vessels within the tumor were labeled by CD34, then the microvessel density (MVD) was calculated. RESULTS: Total positive expression rates of CXCR4 and VEGF were 95% (38/40) and 85% (34/40) respectively. The expression rates of CXCR4 and VEGF were found positive obviously in hemangioblastomas compared with the normal cerebellar tissues (P < 0.01). CXCR4 expression was located in the nucleus of tumor stromal cells. VEGF expression was located in the cytoplasm and membrane of tumor stromal cells and some endothelial cells. VEGF has significant positive correlation with the expression level of CXCR4 (r = 0.704, P <0.001). MVD also has significant positive correlation with the expression level of CXCR4 and VEGF (P < 0.001). But there is no significant difference between the cystic and solid tumors, VHL disease and sporadic disease on the expression level of CXCR4, VEGF and MVD (P > 0.05). CONCLUSION: CXCR4 and VEGF may collaborate to induce angiogenesis in hemangioblastomas.

Management of Dumbbell and Paraspinal Tumors of the Thoracic Spine Using a Single-stage Posterolateral Approach: Case Series.

This study investigated the surgical results of a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy for the management of dumbbell tumors and paraspinal tumors of the thoracic spine. From January 2010 to March 2017, 14 patients with dumbbell tumors or paraspinal tumors of the thoracic spine who underwent resection with single-stage posterolateral approach were followed up and analyzed retrospectively. The operations were performed using a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy without any instrumentation. We reviewed the scores of clinical symptoms and imaging results, including postoperative MRI and reconstructed 3D-CT images. Gross total removal was achieved in 13 patients, and subtotal removal was achieved in 1 case. Histopathology revealed schwannoma in 9 patients, angiolipoma in 1 patient, and paraganglioma and mixed hemangioma in 2 patients each. No significant operative or postoperative complications occurred in any patient. The 14 patients were followed up for 14-68 months (mean 39.4 months). At the final follow-up, no obvious spinal deformity or tumor recurrence was found in any patient except one with paraganglioma. Single-stage posterolateral approach is a good alternative surgical method for removing dumbbell tumors and paraspinal tumors of the thoracic spine without necessitating a subsequent anterior operation.